Kadomatsu al. (Biochem. Biophys. Res. Comm. 151:1312-1318, 1988) isolated and sequenced cDNA from mouse cells, which they referred to as MK1. The corresponding mRNA was said to be abundant in the early stages of mouse embryonic development, but not in later stages. The MK1 protein was suggested as being associated with control of cell differentiation, specifically as a DNA binding protein regulating gene expression. No relationship to any other known protein sequences was found. A subsequent paper (Tomomura et al., J. Biol. Chem. 265:10765-10770, 1990) reported the expression of the MK gene in early stages of embryonal carcinoma cell differentiation, and also noted the occurrence of three distinct classes of cDNA clones, referred to as MK1, MK2 and MK3. Kadomatsu et al. (J. Cell. Biol. 110:607-616, 1990) suggested MK may play a fundamental role in the differentiation of a variety of cells, and that it may be involved in the generation of epithelial tissues and in the remodeling of mesoderm.
The mouse MK1 sequence has now been found to have a high degree of homology in the group of proteins known as heparin-binding neurotrophic factors (HBNFs); the nucleotide sequence encoding the latter proteins has been disclosed in applicants' copending and cofiled U.S. Ser. No. 07/568,574. The HBNF proteins were originally disclosed as HBBMS, in EP 325076. It has now been unexpectedly discovered that a gene corresponding to the mouse MK sequence is also found in human brain. The present invention provides the entire sequence of the gene encoding the human protein, as well as the predicted amino acid sequence of the mature protein, cloning and expression vectors, and host cells capable of expressing the gene and producing pure MK protein. In view of the strong homology between the MK proteins and HBNF, it is likely that these constitute a family of genes and proteins having developmental significance.